Study On Hypervalent Iodine-Mediated Cyclization Of Indole Derivatives

Pyrido[2,3-b]indoles are widely present in many natural products and some drugs,exhibiting high biological activities.Spirooxindole-?-butyrolactones possess good anticancer activity and are key intermediates in the synthesis of various bioactive molecules.This thesis is focus on the preparation of pyrido[2,3-b]indoles and spirooxindole-?-butyrolactones.Based on previous work,we designed intramolecular cyclizations to synthesize above mentioned scaffolds,in which terminal group of side chain worked as a nucleophile.A series of substrates with different terminal groups(including hydroxyl groups,carboxylic acids,and amides)were successfully prepared.After a series of condition screening,it was found that with 1-chloro-1,2-benziodoxol-3-one,the nitrogen atom at side chain of indole attacked C-2 position of indole to form carbon-nitrogen bond.We then explored the scope of this reaction,and found that both electron-withdrawing groups and the halogens at indoles' benzene ring were all tolerated and gave the desired products in good yields.As for substituents on nitrogen of indole,only electron-withdrawing group(benzene sulfonyl and tbutyloxycarbonyl groups)gave the desired products.Next,we envisioned that similar reaction could be conducted with substrates possessing different nucleophiles.To our surprise,3-(5-bromo-1H-indol-3-yl)propanoic acid produced spirooxindole-?-butyrolactone as the major product when it reacted with 1-chloro-1,2-benziodoxol-3-one.Substrates with electron-withdrawing group and halogen at benzene ring were well tolerated and gave spirooxindole-?-butyrolactones in high yields.Meanwhile,amides could also form spirooxindole-?-butyrolactone under standard reaction conditions.In this thesis,a novel and significant method for the synthesis of a series of pyrido[2,3-b]indoles and spirooxindole-?-butyrolactones with hypervalent reagent was reported.After a series of mechanism study,we proposed the possible reaction mechanism.